We have examined the impact of race and positive family history of type 2 diabetes on glucose/insulin dynamics and the two components of glucose disposal in healthy, first-degree relatives of black and white American patients with type 2 diabetes mellitus who are at a greater risk from the disease and their healthy control subjects. Seventeen black and 15 white relatives were studied. Twenty-two black people and 24 white people, without family history of type 2 diabetes, served as healthy control subjects. Standard oral glucose tolerance test (OGTT) and tolbutamide-modified frequent sampling intravenous glucose tolerance (FSIGT) tests were performed in each subject. Insulin sensitivity index (SI) and glucose effectiveness (SG) were calculated using the MINIMOD method described by Bergman et al. Mean fasting and post-stimulation serum glucose levels were not significantly different in the black and white relatives. However, mean serum insulin responses to oral and/or intravenous stimulation were significantly greater in the blacks than whites, irrespective of positive family history of diabetes. The mean SI was significantly (P < 0.02) lower (52%) in the black (3.67 +/- 0.56) than the white [7.50 +/- 1.93 x 10(-4) min-1 (mU1)-1] relatives. Comparing the healthy controls, the mean SI was significantly (P < 0.02) lower (51%) in black than white controls (4.84 +/- 0.78 vs. 9.71 +/- 1.27 x 10 min-1(mU1)-1]. Mean SG and KG were greater (P < 0.05) in the blacks than whites, irrespective of family history of diabetes.(ABSTRACT TRUNCATED AT 250 WORDS)